Real-World Evidence for COVID-19 Delta Variant's Effects on the Digestive System and Protection of Inactivated Vaccines from a Medical Center in Yangzhou, China: A Retrospective Observational Study.

Background: Coronavirus disease 2019 (COVID-19) is rapidly disseminated worldwide, and it continues to threaten global public health. Recently, the Delta variant has emerged as the most dreaded variant worldwide. COVID-19 predominantly affects the respiratory tract, and studies have reported the transient effects of COVID-19 on digestive system function. However, the relationship between the severity of the Delta variant and digestive system function remains to be investigated. Additionally, data on the ability of the inactive Chinese vaccines (Sinovac or Sinopharm) to protect against the Delta variant or COVID-19-induced gastrointestinal symptoms in the real world are insufficient. Thus, the present retrospective observational study first attempted to use the total gastrointestinal symptom rating scale scores (GSRS) to quantify the possible changes in digestive system functions following the Delta variant infection in the early stage. In addition, the study discusses the potential of inactivated vaccines in preventing severe or critical symptoms or Delta variant-induced digestive system dysfunction. Methods: To evaluate the difference between mild illness group, moderate illness group, and severe or critical illness group, analysis of variance (ANOVA) was employed to compare the three groups' total gastrointestinal symptom rating scale scores (GSRS). A chi-squared test was used to compare the differences in the ratio of the abnormal biochemical measurements among the three groups first. Then, the percentage of the vaccinated population was compared among the three groups. Additionally, the ratio of the abnormal serum markers between the vaccinated and nonvaccinated cohorts was compared. A P value < 0.05 was considered statistically significant. Results: Significant differences were observed in the abnormal ratio of alanine aminotransferase (ALT), total bilirubin (TBIL), direct bilirubin (DBIL), lactate dehydrogenase (LDH), and Interleukin 6 (IL-6) ratio among the three groups (P < 0.05). Additionally, no significant difference was observed in the abnormal serum markers ratio between day 14 and day 21 after treatment (P > 0.05). A significant difference was observed in the total GSRS scores among the three groups and the ratio of the vaccinated population among the three groups (P < 0.05). A significant difference was observed in the ratio of the abnormal serum ALT and AST levels between the vaccinated and nonvaccinated cohorts (P < 0.05). Conclusions: In summary, serum AST, DBIL, LDH, and IL-6 levels are potential markers for distinguishing severe or critical patients in the early stage of the Delta variant infection. Additionally, changes in the levels of these serum makers are transient, and the levels can return to normal after treatment. Furthermore, severe gastrointestinal discomfort was significantly more prevalent in patients with severe or critical diseases and should thus be considered in patients diagnosed with Delta variant infection. Finally, inactivated vaccines may prevent severe or critical symptoms and Delta variant-induced liver dysfunction. Vaccination programs must be promoted to protect public health.

Association Between Anti-diabetic Agents and Clinical Outcomes of COVID-19 in Patients with Diabetes: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: During the current Coronavirus Disease 2019 (COVID-19) pandemic, patients with diabetes face disproportionately more. This study was performed to clarify anti-inflammatory effects of anti-diabetic agents on COVID-19 in patients with diabetes. METHODS AND RESULTS: Relevant literature was searched on 15 databases up to November 14, 2020 and was updated on April 13, 2021. The pooled ORs along with 95% CIs were calculated to evaluate combined effects. 31 studies with 66,914 patients were included in qualitative and quantitative synthesis. Meta-analysis showed that metformin was associated with a statistically significant lower mortality (pooled OR = 0.62, 95% CI, 0.50-0.76, p = 0.000) and poor composite outcomes (pooled OR = 0.83, 95% CI, 0.71-0.97, p = 0.022) in diabetic patients with COVID-19. Significance of slight lower mortality remained in sulfonylurea/glinides (pooled OR = 0.93, 95% CI, 0.89-0.98, p = 0.004), but of poor composite outcomes was not (pooled OR = 1.48, 95% CI, 0.61-3.60, p = 0.384). Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) were associated with statistically non-significant lower mortality (pooled OR = 0.95, 95% CI, 0.72-1.26, p = 0.739) or poor composite outcomes (pooled OR = 1.27, 95% CI, 0.91-1.77, p = 0.162) of COVID-19 in diabetic patients. CONCLUSION: Metformin might be beneficial in decreasing mortality and poor composite outcomes in diabetic patients infected with SARS-CoV-2. DPP-4 inhibitors, sulfonylurea/glinides, SGLT-2 inhibitors, and GLP-1RA would not seem to be adverse. There was insufficient evidence to conclude effects of other anti-diabetic agents. Limited by retrospective characteristics, with relative weak capability to verify causality, more prospective studies, especially RCTs are needed. REGISTRATION NUMBER: PROSPERO-CRD42020221951.

Is DPP-4 Use Associated With a Decreased Mortality for COVID-19 Diabetic Patients? A Meta-Analysis

Introduction: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Dipeptidyl peptidase-4 (DPP-4) is a multi-expressed glycoprotein that is speculated to be a functional SARS-CoV-2 receptor. Previous studies remain controversial regarding whether DPP-4 use is associated with reduced risk for COVID-19 diabetic patients. Thus, this meta-analysis is performed. Method: A comprehensive literature search on PubMed was conducted to identify all relevant studies published prior to October 2020. This meta-analysis was reported in conformity to the Preferred Reporting Project declared by the Systematic Review and Meta-Analysis (PRISMA). The quality assessment was performed by the Newcastle-Ottawa Scale (NOS). The pooled odds ratio (OR) and 95% confidence intervals (CI) were calculated. Random-effect model or fixed-effect model was used based on heterogeneity. Subgroup analyses were performed based on types of diabetes, geographic locations, study designs, and different sample sizes. Sensitivity analysis and publication bias detection were also performed. All statistical analyses were performed using RevMan and STATA 12.0 statistical software, and all P values were two-tailed, the test level was 0.05. Result: 69 articles were obtained. 5 articles involving 49,989 participants were included. All included studies were considered moderate to high quality. No decreased mortality of COVID-19 diabetic patients was found among DPP-4 users (OR 0.86, 95%CI: 0.22,3.41, P=0.083, I2=81%). In the subgroup analysis, studies in Asia (OR 3.11, 95%CI: 0.78, 12.34, P=0.001, I2=70%) did not found reduced mortality, whereas studies in Europe (OR 0.36, 95%CI: 0.23, 0.56, P&lt;0.00001, I2=0%) were associated with reduced mortality. Based on study designs, the four case-control studies (OR 1.27, 95%CI: 0.27, 5.93, P=0.76, I2=89%) did not find reduced mortality, but one cohort study (OR 0.13, 95%CI: 0.02, 0.84, P=0.03) showed a reduced mortality. The four studies investigating Type 2 Diabetes Mellitus (T2DM) did found reduced mortality (OR 0.74, 95%CI: 0.13, 4.24, P=0.73, I2=90%). For sample size &gt;200, reduced risk of mortality (OR 0.28, 95%CI: 0.07, 1.15, P=0.08, I2=32%) was found, however, for sample ≤200, no statistically significant association (OR 1.44, 95%CI: 0.23, 8.89, P=0.70, I2=93%) was found. Sensitivity analysis by changing models and omitting each study at a time confirm the stability of the result. Begg’s test (z=-0.24, P=1.000) and Egger’s test (t=0.56, P=0.618) did not detect a significant risk of publication bias. Conclusion: The current meta-analysis did not find reduced mortality for COVID-19 diabetic patients who take DPP-4. However, subgroup-analyses found reduced mortality in Europe. More high-quality original studies are needed to further explore the association between DPP-4 use and the mortality risk of COVID-19.

Association of smoking history with severe and critical outcomes in COVID-19 patients: A systemic review and meta-analysis.

INTRODUCTION: The highly infectious coronavirus disease 2019 (COVID-19) has now rapidly spread around the world. This meta-analysis was strictly focused on the influence of smoking history on the severe and critical outcomes on people with COVID-19 pneumonia. METHODS: A systematic literature search was conducted in eight online databases before 1 February 2021. All studies meeting our selection criteria were included and evaluated. Stata 14.0 software was used to analyze the data. RESULTS: A total of 109 articles involving 517,020 patients were included in this meta-analysis. A statistically significant association was discovered between smoking history and COVID-19 severity, the pooled OR was 1.55 (95%CI: 1.41-1.71). Smoking was significantly associated with the risk of admission to intensive care unit (ICU) (OR=1.73, 95%CI: 1.36-2.19), increased mortality (OR=1.58, 95%CI: 1.38-1.81), and critical diseases composite endpoints (OR=1.61, 95%CI: 1.35-1.93), whereas there was no relationship with mechanical ventilation. The pooled prevalence of smoking using the random effects model (REM) was 15% (95%CI: 14%-16%). Meta-regression analysis showed that age (P=0.004), hypertension (P=0.007), diabetes (P=0.029), chronic obstructive pulmonary disease (COPD) (P=0.001) were covariates that affect the association. CONCLUSIONS: Smoking was associated with severe or critical outcomes and increased the risk of admission to ICU and mortality in COVID-19 patients, but not associated with mechanical ventilation. This association was more significant for former smokers than in current smokers. Current smokers also had a higher risk of developing severe COVID-19 compared with non-smokers. More detailed data, which are representative of more countries, are needed to confirm these preliminary findings.

Face masks to prevent transmission of COVID-19: A systematic review and meta-analysis.

BACKGROUND: Based on the status of the COVID-19 global pandemic, there is an urgent need to systematically evaluate the effectiveness of wearing masks to protect public health from COVID-19 infection. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement was consulted to report this systematic review. We conducted a systematic review and meta-analysis to evaluate the effectiveness of using face masks to prevent the spread of SARS-CoV-2. Relevant articles were retrieved from PubMed, Web of Science, ScienceDirect, Cochrane Library, and Chinese National Knowledge Infrastructure, VIP (Chinese) database. There were no language restrictions. This study was registered with PROSPERO under the number CRD42020211862. RESULTS: A total of 6 studies were included, involving 4 countries, after a total of 5,178 eligible articles were searched in databases and references. In general, wearing a mask was associated with a significantly reduced risk of COVID-19 infection (OR = 0.38, 95% CI: 0.21-0.69, I2 = 54.1%). For the healthcare workers group, masks were shown to have a reduced risk of infection by nearly 70%. Sensitivity analysis showed that the results were robust. CONCLUSIONS: The results of this systematic review and meta-analysis support the conclusion that wearing a mask could reduce the risk of COVID-19 infection. Robust randomized trials are needed in the future to better provide evidence for these interventions.

Efficacy of face mask in preventing respiratory virus transmission: A systematic review and meta-analysis.

BACKGROUND: Conflicting recommendations exist related to whether masks have a protective effect on the spread of respiratory viruses. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was consulted to report this systematic review. Relevant articles were retrieved from PubMed, Web of Science, ScienceDirect, Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI), VIP (Chinese) database. RESULTS: A total of 21 studies met our inclusion criteria. Meta-analyses suggest that mask use provided a significant protective effect (OR = 0.35 and 95% CI = 0.24-0.51). Use of masks by healthcare workers (HCWs) and non-healthcare workers (Non-HCWs) can reduce the risk of respiratory virus infection by 80% (OR = 0.20, 95% CI = 0.11-0.37) and 47% (OR = 0.53, 95% CI = 0.36-0.79). The protective effect of wearing masks in Asia (OR = 0.31) appeared to be higher than that of Western countries (OR = 0.45). Masks had a protective effect against influenza viruses (OR = 0.55), SARS (OR = 0.26), and SARS-CoV-2 (OR = 0.04). In the subgroups based on different study designs, protective effects of wearing mask were significant in cluster randomized trials and observational studies. CONCLUSIONS: This study adds additional evidence of the enhanced protective value of masks, we stress that the use masks serve as an adjunctive method regarding the COVID-19 outbreak.